The Opioid Crisis: Treating Opioid Withdrawal in the Emergency Department

Dr. David Vearrier, Program Director Medical Toxicology Fellowship Drexel University College of Medicine, joins me to discuss the physiology of opioid withdrawal and approaches to treatment including suboxone and other approaches.

this slide really caught my attention because I’ve been discussing the relationship between bup and naloxone for a while with a group of bup experts and there is a lot of disagreement on this subject. wondering if any of you have any science (or even anecdote) to support your assertion here. I’m not challenging the assertion, just looking for literature on this subject. -reuben

Heh, thanks. Lewis is one of the folks I’ve been talking to about this. I’ve pasted the relevant passage from that paper below. Bup has such fantastically complex pharmacology, I wonder if we’ll ever be able to develop a sound strategy for managing buprenorphine-precipitated withdrawal (BPW) across the spectrum of different patient presentations (and the pharmacology they come in with) and bup doses.

And the relationship between bup and naloxone is super-complex. I’m not terribly concerned with bup toxicity, am more interested in transitioning patients with NPW (naloxone-precipitated withdrawal) to bup MAT in the ED.

Thanks for the reference.

reuben

3.2 Naloxone and buprenorphine
In healthy volunteers, buprenorphine’s extremely high μ-receptor affinity (Kd: 0.08 – 0.22 nM) and its correspond- ing slow association and dissociation rate from the μ-receptor (receptor dissociation half-life [t1/2 koff]: 41 – 68 min) were associated with a delayed onset of action of naloxone in reversing the buprenorphine-induced ventilatory depression compared with that of fentanyl (Kd: 3.39 μM; t1/2 koff: 2 mg) were required to reverse buprenorphine- induced ventilatory depression [40,42]. But, the administration of > 4 mg of naloxone showed an inverse dose-response rela- tionship, accompanied by significant decreases in the reversal of buprenorphine-induced ventilatory depression [40,42]. This finding has been theoretically attributed to the non- competitive auto-inhibition of two μ-receptor subpopulations by buprenorphine in which one mediates the agonist effect at low doses and the other mediates the antagonist effect at high doses [42,77,78]. Similar delay in the reversal of ventilatory depression with naloxone was also observed between morphine (t1/2 koff: 5 min) and its active metabolite, morphine-6-glucuronide (t1/2 koff: 21 min). In this situation, the reversal of morphine-6-glucuronide-induced ventilatory depression with naloxone was slower by ~ 30 min, compared with that of morphine [35].